Key result
Targeted capture and massive parallel sequencing identified a novel pathogenic KCNH2 mutation (c.2038delG) in a large LQTS family that was initially missed by DHPLC due to allelic dropout.
Why the study?
Does targeted capture and massive parallel sequencing identify pathogenic mutations missed by DHPLC in genotype-negative LQTS families?
Case Report
Does targeted capture and massive parallel sequencing identify pathogenic mutations missed by DHPLC in genotype-negative LQTS families?
Repeat genetic testing with massive parallel sequencing is crucial in robust cases of LQTS that remain genotype negative with older mutation scanning techniques.
We present a new mutation in KCNH2 (c.2038delG) resulting in a frameshift and premature truncation of the IKr channel protein in a large LQTS family with several sudden death cases. This mutation was initially missed by mutation scanning with DHPLC due to allelic dropout and only retrieved after repeat genetic testing with targeted capture and massive parallel sequencing. There was full penetrance of this mutation, only if an individualized QT correction derived from 24-hour Holter data was used. This case again underscores the importance of repeat genetic testing in robust cases of LQTS that remained genotype negative with mutation scanning techniques.
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Robyns et al. (2015) conducted a case report in Long QT Syndrome (LQTS). Targeted capture and massive parallel sequencing vs. Mutation scanning with DHPLC was evaluated on Detection of pathogenic mutation. Targeted capture and massive parallel sequencing identified a novel pathogenic KCNH2 mutation (c.2038delG) in a large LQTS family that was initially missed by DHPLC due to allelic dropout.
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